Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer

Abstract

Background: Patients with pancreatic cancer have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) produces localised tissue necrosis but previous studies using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC) caused prolonged skin photosensitivity. This study assessed a shorter acting photosensitiser, verteporfin.

Methods: Fifteen inoperable patients with locally advanced cancers were sensitised with 0.4 mg kg(-1) verteporfin. After 60-90 min, laser light (690 nm) was delivered via single (13 patients) or multiple (2 patients) fibres positioned percutaneously under computed tomography (CT) guidance, the light dose escalating (initially 5 J, doubling after each three patients) until 12 mm of necrosis was achieved consistently.

Results: In all, 12 mm lesions were seen consistently at 40 J, but with considerable variation in necrosis volume (mean volume 3.5 cm(3) at 40 J). Minor, self-limiting extrapancreatic effects were seen in multifibre patients. No adverse interactions were seen in patients given chemotherapy or radiotherapy before or after PDT. After PDT, one patient underwent an R0 Whipple's pancreaticoduodenectomy.

Conclusions: Verteporfin PDT-induced tumour necrosis in locally advanced pancreatic cancer is feasible and safe. It can be delivered with a much shorter drug light interval and with less photosensitivity than with older compounds.

Figure 1

CT scans from patient 13 undergoing verteporfin PDT. The image on the left shows a baseline contrast-enhanced CT with a low attenuation mass in the head of the pancreas. The centre image shows percutaneous needle placement into the tumour. The image on the right shows the day 5 post PDT contrast-enhanced CT with a 2.67-cm³ zone of necrosis in the region of the pancreatic head (arrowed).

Figure 2

Necrosis measurements following verteporfin PDT in patient 4. (A) A single axial slice of the pancreas from the post-treatment CT scans. The arrow indicates the area of necrosis within the pancreas. (B) The same slice showing segmentation of the necrotic tissue in pink. (C) Volume rendering of segmentation of the necrotic zone. (D) The volume of the necrotic tissue region is shown for each patient in the study, as determined from the segmentation of the post-treatment CT scans. Total energy delivered is shown for each patient. For patient 14, two fibres of 1-cm diffuser length each delivering 40 J cm⁻¹ were used. For patient 15, three fibres of 2-cm diffuser length each delivering 40 J cm⁻¹ were used. Patient 12 is not included in this figure as necrosis was present before treatment and therefore the effect of treatment could not be assessed.

Figure 3

Kaplan–Meier curve showing the cumulative survival from treatment with PDT in all patients.

Figure 4

CT scan from patient 7 who had a successful Whipple's resection following PDT. (A) Image from CT before PDT showing tumour abutting the superior mesenteric artery (block arrow). (B) Four weeks after PDT, the repeat CT scan at the same level suggested that there was a clear tissue plane between the artery and the tumour (block arrow), so rendering him suitable for surgery. As these scans were at the level of maximum tumour involvement of the artery, they are not exactly at the same level as the PDT necrosis, which is not visible on scan (B).

Figure 5

Pancytokeratin immunohistochemistry section of pancreatic cancer from patient 7 who underwent a Whipple's pancreaticoduodenectomy 5 weeks after PDT. The patient received radiotherapy 5 months before PDT, causing fibrosis over a wide part of the gland in addition to that inherent to pancreatic adenocarcinomas. However, there is a clearly identifiable central area in this section of the tumour with a markedly reduced number of cells, compared with the surrounding tumour. This corresponds to the PDT-treated area.